We have found that levamisole is a nicotinic depolarizing blocking analog of acetylcholine and that mutants of the nematode C. elegans resistant to levamisole pharmacologically lack functional acetycholine receptors. Derivatives of levamisole suitable for coupling to agarose for affinity chromatography or to proteins for use in binding assays or histochemistry will be prepared and tested pharmacologically for suitability. O'Farrell bidimensional electrophoresis will also be used to compare iodinated membrane proteins from the wild type and the levamisole-resistant mutants. The use of bidimensional electrophoresis on affinity chromatographed membrane extract should be a powerful means of revealing minute protein differences between the wild type and the mutants. Once alteration of the receptor can be shown, our goal is to further dissect the twelve or so mutant loci into structural, regulatory, and processing genes and thence at the genetic and the molecular level to study these mutants as a model system for synaptic development.